FOXM1 dependent regulation of retinal pigment epithelium cell fate

The integrity of the epithelium is maintained by a complex but regulated interplay of processes that allow seamless orchestration of a proliferative state into a stably differentiated state. In this study, using stem cell derived Retinal Pigment Epithelium (RPE) cells as a model; we have investigated the molecular mechanisms that affect attainment of the epithelial phenotype. We identify a novel role for the proto-oncogene FOXM1 in determining epithelial fate of RPE by directly regulating cell proliferation and by indirectly regulating expression of signalling factors BMP7 and Wnt5B; both of which are intimately required for eventual acquisition of the epithelial phenotype. This study uncovers the role of FOXM1 in a non-oncogenic, native-like setting and shows that human ES derived RPE can serve as a useful model system to address biological questions not restricted to visual function.